Phytol derived immunoadjuvants and their use in vaccine formulations

Abstract

This invention relates to a novel immunoadjuvant, an adjuvant component, and vaccines containing the adjuvant component. The adjuvant includes phytol or a phytol derivative. The adjuvant component, when combined with a soluble or particulate antigen, provides a vaccine with an enhanced ability to induce both humoral and cytotoxic immune responses while displaying reduced toxicity and/or adverse side effects over vaccines that include the antigen but without the benefit of this adjuvant component.

1. An immunogenic composition comprising:
 a vaccine antigen; 
 an adjuvant component comprising phytol, phytanol, or a phytol derivative wherein the phytol derivative is of the following formula: 
 
       
         
           
           
               
               
           
         
         wherein R 1  is selected from the group of chemical moieties, ions, or radicals consisting of: Br − , Cl − , I − , —NH 2 , —NO 2 , OH, PO 4   = , HPO 4   − , NHR 2 , OC(O)R 2 , OR 2 , wherein R 2  is a hydrocarbyl having 1 to 10 carbon atoms or a carbohydrate; 
         wherein the vaccine antigen is homogenously dispersed in the adjuvant component; 
         and optionally a carrier. 
       
     
     
       2. The composition of  claim 1  wherein the adjuvant component comprises phytol. 
     
     
       3. The composition of  claim 1  wherein the adjuvant component comprises phytanol. 
     
     
       4. The composition of  claim 1  wherein the adjuvant component comprises a phytol derivative selected from the group consisting of: phytanol; 3,7,11,15-tetramethyl-1-hexadecanyl acetate; 1-chloro-3,7,11,15-tetramethyl hexadecane; 1-iodo-3,7,11,15-tetramethyl hexadecane; 1-amino-3,7,11,15-tetramethyl hexadecane; 1-methyl amino-3,7,11,15-tetramethyl hexadecane; stereoisomers and mixtures thereof. 
     
     
       5. The composition of  claim 1  wherein the antigen includes a T-independent antigen. 
     
     
       6. The composition of  claim 5  wherein the antigen is selected from the group consisting of polysaccharides, pneumococcus polysaccharides, bacterial lipopolysaccharides, synthetic lipopolysaccharides, and hapten-polysaccharide conjugates. 
     
     
       7. The composition of  claim 1  wherein the vaccine antigen comprises a T-dependent antigen. 
     
     
       8. The composition of  claim 7  wherein the vaccine antigen is selected from the group consisting of: proteins, peptides, lipoproteins, glycoproteins, gangliosides, cerebrosides, nucleoproteins, eukaryotic cellular isolates, and prokaryotic cellular isolates. 
     
     
       9. The composition of  claim 1  wherein the carrier is sterile water at pH 7.0. 
     
     
       10. The composition of  claim 1  wherein the carrier comprises physiological buffers that include carbonates, bicarbonates, phosphates. 
     
     
       11. The composition of  claim 1  wherein the composition is an oil-in-water emulsion. 
     
     
       12. The composition of  claim 11  further comprising a surfactant or emulsifier. 
     
     
       13. The composition of  claim 12  wherein the emulsifier is selected from the group consisting of: phospholipids, lysophosphoglycerides, spingomyelin, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl inositol and mixtures thereof. 
     
     
       14. The composition of  claim 1  wherein the adjuvant component and the vaccine antigen are present at a weight ratio of between about 1:4 to about 1:1. 
     
     
       15. The composition of  claim 1  wherein the composition is in a unit dosage form. 
     
     
       16. The composition of  claim 1  wherein R 1  is Br − , Cl − ; I − ; —NH 2 , —NO 2 , OH, PO 4   = , HPO 4   − , NHR 2 , OC(O)R 2 , OR 2 , wherein R 2  is a hydrocarbyl having 1 to 10 carbon atoms or a carbohydrate. 
     
     
       17. The composition of  claim 1  wherein R 1  is Cl − . 
     
     
       18. The composition of  claim 1  wherein R 1  is I − . 
     
     
       19. The composition of  claim 1  wherein R 1  is —NH 2 . 
     
     
       20. The composition of  claim 1  wherein R 1  is OC(O)R 2  or OR 2 , wherein R 2  is mannitol.